The present invention relates to processes for producing 3,3,3-trifluoro-2-hydroxypropionic acid and its derivatives, which are useful intermediates for medicines and liquid crystals.
There are known the following first to fourth processes for producing 3,3,3-trifluoro-2-hydroxypropionic acid, which is represented by the formula 2. 
In the first process, it is derived from 3,3,3-trifluoro-2-hydroxypropanol or 3,3,3-trifluoropropene-1,2-oxide (see Synlett, 7, pp. 507-508 (1994); and Japanese Patent Application Publications 5-078277 and 5-078278).
In the second process, it is derived from trifluoropyruvate (see Chem. Ber., 125(12), pp. 2795-2802 (1992)).
In the third process, it is derived from trifluoroacetaldehyde (see Japanese Patent Application Publication 3-148249).
In the fourth process, it is derived from hexafluoroisopropanol (see Nippon Kagaku Kaishi No. 9, pp. 1576-1586 (1989)).
Other processes for producing 3,3,3-trifluoro-2-hydroxypropionic acid are disclosed in Japanese Patent Application Publications 2002-080429 and 2001-226316; Organic Letters, 3(3), pp. 457-459 (2001); Tetrahedron Letters, 41(23), pp. 4603-4607 (2000), and Tetrahedron Letters, 41(22), pp. 4507-4512 (2000).
Although it is possible to obtain 3,3,3-trifluoro-2-hydroxypropionic acid with a relatively high yield by the above conventional processes, the raw materials (i.e., trifluoromethyl-containing compounds) used in these processes have very high prices. Therefore, these processes are not suitable for industrially producing 3,3,3-trifluoro-2-hydroxypropionic acid.
The following reaction scheme is taught in WO 02/00601 corresponding to European Patent Application EP 1300391 A1; WO 00/55113 corresponding to U.S. Patent Application Publication 2002/0026081 A1; Huaxue Gongcheng (Xilan, China), 28(4), pp. 44-45, 51 (2000); Japanese Patent Application Publication 10-139724; WO 98/07687 corresponding to U.S. Pat. No. 6,020518; J. Indian Chem. Soc., 66(4), pp. 239-240 (1989); J. Antibiot., 40(11), pp. 1555-1562 (1987); Tetrahedron, 37(17), pp. 3061-3065 (1981); Yukagaku, 28(7), pp. 501-502 (1979); and German Patent Application Publication 2648300 corresponding to U.S. Pat. No. 4,052,460. 
Furthermore, it is disclosed in Chem. Ber., 125(12), pp. 2795-2802 (1992) that 3,3,3-trifluoro-2-hydroxypropionic acid alkyl ester is protected at its hydroxyl group (bonded to the second carbon) with a THP (tetrahydropyranyl) group, and then its alkoxycarbonyl group (xe2x80x94COOR) is reduced to a hydroxymethyl group (xe2x80x94CH2OH) using lithium aluminum hydride. Then, it is necessary to conduct a deprotection to produce 3,3,3-trifluoro-2-hydroxypropanol. Thus, the process of this publication is cumbersome for industrial production.
Japanese Patent Application Publication 2000-063306 discloses that 1,1-dichloro-3,3,3-trifluoroacetone is hydrolyzed in the presence of disodium hydrogenphosphate to trifluoropropanetetraol. It is further disclosed in this publication that the hydrolysis is conducted at a pH of from 2 to 9.
Japanese Patent Application Publication 5-70406 discloses a process for producing a xcex2, xcex2,xcex2-trifluorolactic acid ester by reacting xcex2,xcex2,xcex2-trifluorolactic acid with an alcohol (having a carbon atom number of at least 3) in the presence of a catalyst.
It is an object of the present invention to provide a process for efficiently producing 3,3,3-trifluoro-2-hydroxypropionic acid or its derivative(s), which are useful intermediates for medicines and liquid crystals.
According to the present invention, there is provided a process for producing 3,3,3-trifluoro-2-hydroxypropionic acid represented by the formula 2. This process includes the step of (a) bringing a 1,1-dihalogeno-3,3,3-trifluoroacetone represented by the formula 1 into contact with a basic aqueous solution (for example, having a pH of 12 or higher), 
wherein X is Cl, Br or I.
The above raw material, 1,1-dihalogeno-3,3,3-trifluoroacetone, is industrially available with a low price.
It is possible to convert 3,3,3-trifluoro-2-hydroxypropionic acid into 3,3,3-trifluoro-2-hydroxypropanol represented by the formula 4 almost quantitatively, by a process including the steps of:
(b) reacting the 3,3,3-trifluoro-2-hydroxypropionic acid, which has been obtained by the above step (a), with a lower alcohol represented by the formula 5, under an acidic condition, thereby producing a 3,3,3-trifluoro-2-hydroxypropionate represented by the formula 3; and
(c) reacting the 3,3,3-trifluoro-2-hydroxypropionate with a hydride reducing agent, thereby producing the 3,3,3-trifluoro-2-hydroxypropanol, 
wherein R is a C1-C6 lower alkyl group.
It is possible by the above step (c) to efficiently reduce the alkoxycarbonyl group (xe2x80x94CO2R) into the hydroxymethyl group (xe2x80x94CH2OH) using a hydride reducing agent (e.g., sodium borohydride), without necessity of protecting the hydroxyl group (bonded to the second carbon) of the raw material, 3,3,3-trifluoro-2-hydroxypropionate and without necessity of the following deprotection. Thus, it is possible to easily obtain 3,3,3-trifluoro-2-hydroxypropanol with high yield and less load in industrial production.
The above-mentioned exemplary hydride reducing agent, sodium borohydride, is low in price and easy for handling. Thus, this sodium borohydride is considerably superior in safety and economy to lithium aluminum hydride.